Project

Back to overview

Investigation into the role of IL-19 producing macrophages in intestinal inflammation

Applicant Niess Jan Hendrik
Number 146290
Funding scheme Project funding (Div. I-III)
Research institution Abt. für Gastroenterologie und Hepatologie Universitätsspital Basel
Institution of higher education University of Berne - BE
Main discipline Internal Medicine
Start/End 01.12.2013 - 30.11.2016
Approved amount 309'411.00
Show all

Keywords (3)

IL-19; Darmimmunität; Makrophagen

Lay Summary (German)

Lead
Funktion von Makrophagen gebildeten IL-19 bei Regulation einer Darmentzündung
Lay summary
Chronisch entzündliche Darmerkrankungen sind häufige Erkrankungen, die im jungen Erwachsenenalter auftreten und erheblich die Lebensqualität der Betroffenen einschränkt. Ursachen der chronisch entzündlichen Darmerkrankungen sind nicht geklärt. In diesem Projekt werden wir die Zusammensetzung von dendritischen Zellen und Makrophagen in der Lamina propria des Dickdarmes charakterisieren. Dendritische Zellen und Makrophagen sind „Fresszellen“, die eingedrungene Bakterien aufnehmen und beseitigen. Die Klassifikation der Makrophagen und dendritischen Zellen im Kolon wird aktuell kontrovers diskutiert. Wir werden untersuchen, ob intestinale Makrophagen das Interleukin 19 produzieren und ob dies den Verlauf einer Darmentzündung in Entzündungsmodellen des angeborenen und erworbenen Abwehrsystems beeinflusst.
Direct link to Lay Summary Last update: 08.11.2013

Responsible applicant and co-applicants

Employees

Name Institute

Publications

Publication
The Interleukin-20 Cytokines in Intestinal Diseases
Niess Jan Hendrik, Hruz Petr, Kaymak Tanay (2018), The Interleukin-20 Cytokines in Intestinal Diseases, in Frontiers in Immunology, 9, 1-9.
Injections of Lipopolysaccharide into Mice to Mimic Entrance of Microbial-derived Products After Intestinal Barrier Breach
Raduolovic Katarina, Mak’Anyengo Rachel, Kaya Berna, Steinert Anna, Niess Jan Hendrik (2018), Injections of Lipopolysaccharide into Mice to Mimic Entrance of Microbial-derived Products After Intestinal Barrier Breach, in Journal of Visualized Experiments, (135), 135.
The Stimulation of Macrophages with TLR Ligands Supports Increased IL-19 Expression in Inflammatory Bowel Disease Patients and in Colitis Models.
Steinert Anna, Linas Ioannis, Kaya Berna, Ibrahim Mohamed, Schlitzer Andreas, Hruz Petr, Radulovic Katarina, Terracciano Luigi, Macpherson Andrew J, Niess Jan Hendrik (2017), The Stimulation of Macrophages with TLR Ligands Supports Increased IL-19 Expression in Inflammatory Bowel Disease Patients and in Colitis Models., in The Journal of Immunology, 199(7), 2570-2584.
IL26 modulates cytokine response and anti-TNF consumption in Crohn's disease patients with bacterial DNA
Piñero Paula, Juanola Oriol, Gutiérrez Ana, Zapater Pedro, Giménez Paula, Steinert Anna, Sempere Laura, González-Navajas José M., Niess Jan H., Francés Rubén (2017), IL26 modulates cytokine response and anti-TNF consumption in Crohn's disease patients with bacterial DNA, in J Mol Med, 95(11), 1227-1236.
Development of an Antigen-driven Colitis Model to Study Presentation of Antigens by Antigen Presenting Cells to T Cells.
Rossini Valerio Radulovic Katarina Riedel Christian U. Niess Jan Hendrik (2016), Development of an Antigen-driven Colitis Model to Study Presentation of Antigens by Antigen Presenting Cells to T Cells., in J Vis Exp, (115), e54421.
Gastro-intestinal tract: The leading role of mucosal immunity.
Steinert Anna Radulovic Katarina Niess. Jan J (2016), Gastro-intestinal tract: The leading role of mucosal immunity., in Swiss Med Wkly, 146, w14293.

Collaboration

Group / person Country
Types of collaboration
Andreas Schlitzer, Life and Medical Science Institute, University of Bonn, Germany Germany (Europe)
- in-depth/constructive exchanges on approaches, methods or results

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
European Mucosal Immunology Group Meeting Poster Increased Interleukin-19 Expression in IBD Patients and Colitis Models Suggests Immunosuppressive Function 19.10.2016 Copenhagen, Denmark Steinert Anna; Niess Jan Hendrik;
Annual Congress SGG - SGVC-SASL Poster The cytokine IL-19 is expressed by macrophages 01.10.2016 Interlaken, Switzerland Niess Jan Hendrik;
Annual Congress SGG -SGVC - SASL Poster Increased IL-19 Expression in IBD Patients and Colitis Models Indicate Immunosuppressive Function 22.09.2016 Interlaken, Switzerland Niess Jan Hendrik;
Wolfsberg PhD Meeting Talk given at a conference Induction of Interleukin-19 in a Mouse Model of Colitis 09.02.2016 Wolfsberg, Switzerland Steinert Anna;
Graduate School for Cellular and Biomedical Sciences (GCB) 10th Anniversary Symposium 2016 Poster Induction of Interleukin-19 in the Colon Lamina Propria in a Model of Dextran Sodium Sulfate-induced Colitis 04.02.2016 Bern, Switzerland Steinert Anna;
Seminar Institute Pasteur de Lille Individual talk Intestinal Monocyte and Macrophages in Host Defence 08.01.2016 Lille, France Niess Jan Hendrik;
Departement Klinische Forschung Research Day Poster The Expression of Interleukin-19 Distinguishes CX3CR1-positive Macrophages from Dendritic Cells 04.11.2015 Bern, Switzerland Steinert Anna;
17th International Congress Mucosal Immunology Talk given at a conference The Expression of Interleukin-19 Distinguishes CX3CR1-positive Macrophages from Dendritic Cells 14.07.2015 Berlin, Germany Niess Jan Hendrik;
ENII Summer School; Porto Cervo, Olbia Poster The Expression of Interleukin-19 Distinguishes CX3CR1-positive Macrophages from Dendritic Cells 12.05.2015 Porto Cervo, Olbia, Italy Steinert Anna;
Progress Report, Departement Klinische Forschung, University of Bern Individual talk The Role of IL-19 in Intestinal Homeostasis 06.05.2015 Bern, Switzerland Steinert Anna;
Wolfsberg Ph.D. meeting Talk given at a conference The Expression of Interleukin-19 Distinguishes CX3CR1-positive Macrophages from Dendritic Cells 25.02.2015 Wolfsberg, Switzerland Steinert Anna;


Awards

Title Year
Travel grant, the European Mucosal Immunology Group (EMIG) meeting, Copenhagen, Denmark, October 2016. 2016
Travel grant, the European Network of Immunology Institutes (ENII) Summer School, Porto Cervo, Olbia, Italy, May 2015 2015

Associated projects

Number Title Start Funding scheme
175548 Intestinal macrophages and dendritic cells in oral tolerance and colitis 01.09.2018 Project funding (Div. I-III)
170809 Super Resolution and Endoscopic Two Photon Microscopy - Imaging of Cell Migration in Inflammation, Metastasis and Regeneration 01.01.2017 R'EQUIP

Abstract

BACKGROUNDAlthough several subsets of mononuclear cells have been described in the lamina propria of the small and large intestine, mononuclear phagocytes have remained a rather undefined cell population. The development and analysis of fluorescent reporter mouse lines has led to the identification of CX3CR1+ mononuclear phagocytes in the intestine, which sample luminal microbes by extending processes into the intestinal lumen (Science 2005;307, 254). The characterization of CX3CR1+ mononuclear phagocytes has revealed that CX3CR1+ phagocytes are a heterogeneous cell population (J Immunol 2010; 180, 559), that can be distinguished in mononuclear phagocytes with high CX3CR1 or low CX3CR1 expression. Mononuclear phagocytes with high CX3CR1 expression express F4/80 and the tissue macrophage marker CD68 indicating a macrophage-like phenotype, produce IL-10, expand regulatory T cells in oral tolerance models and suppress T cells during transfer colitis. Mononuclear phagocytes with low CX3CR1 expression induce the differentiation of IFN-gamma secreting Th1 and IL-17A producing Th17 cells. Published work and our own results have indicated that macrophages produce the IL-10 type cytokine IL-19 and that the absence of IL-19 signalling in IL-20R2-/- animals is associated with accelerated colitis indicating that the IL-10 type cytokine IL-19 plays a role in the regulation of intestinal inflammation. OBJECTIVESIn this grant we will address if mononuclear phagocytes with high and low CX3CR1 expression differentially express IL-19 and mononuclear phagocyte-derived IL-19 suppresses intestinal inflammation. 1. The mononuclear phagocyte that produces IL-19 will be defined. 2. The role of phagocyte-derived IL-19 will be elucidated in innate colitis. 3. The suppression of T cell induced colitis by phagocyte derived IL-19 will be determined.METHODSTo identify IL-19+ phagocytes in the intestinal lamina propria we have generated IL-19TdTomato transgenic mice, in which the IL-19 promoter drives the expression of the red fluorescent protein TdTomato. After the identification of the cell that produces IL-19 we determine the role of phagocyte derived IL-19 in regulating intestinal inflammation with CD40 induced (innate) and T cell driven colitis models.SIGNIFICANCE The CX3CR1+ phagocyte - IL-19 system is critical for the maintenance of intestinal homeostasis, but poorly understood. In this grant the mononuclear cell that produces the IL-10 type cytokine IL-19 will be identified with help of novel mouse models, in which the IL-19 promoter drives the expression of the red fluorescent protein TdTomato and the importance of phagocyte-derived IL-19 for innate or T cell-driven colitis determined. The production of IL-19 by mononuclear cells after recognition of intestinal microbes could elucidate principles by which the mucosal immune system achieves the co-existence between the intestinal microflora and the host. An improved understanding of the CX3CR1+ phagocyte - IL-19 system has implications for our knowledge on the development of inflammatory bowel disease.
-